Prenatal cannabis exposure is associated with alterations in offspring DNA methylation at genes involved in neurodevelopment, across the life course.

Prenatal cannabis exposure (PCE) is of increasing concern globally, due to the potential impact on offspring neurodevelopment, and its association with childhood and adolescent brain development and cognitive function. However, there is currently a lack of research addressing the molecular impact of PCE, that may help to clarify the association between PCE and neurodevelopment. To address this knowledge gap, here we present epigenome-wide association study data across multiple time points, examining the effect of PCE and co-exposure with tobacco using two longitudinal studies, the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Christchurch Health and Development Study (CHDS) at birth (0 y), 7 y and 15-17 y (ALSPAC), and ~27 y (CHDS). Our findings reveal genome-wide significant DNA methylation differences in offspring at 0 y, 7 y, 15-17 y, and 27 y associated with PCE alone, and co-exposure with tobacco. Importantly, we identified significantly differentially methylated CpG sites within the genes LZTS2, NPSR1, NT5E, CRIP2, DOCK8, COQ5, and LRP5 that are shared between different time points throughout development in offspring. Notably, functional pathway analysis showed enrichment for differential DNA methylation in neurodevelopment, neurotransmission, and neuronal structure pathways, and this was consistent across all timepoints in both cohorts. Given the increasing volume of epidemiological evidence that suggests a link between PCE and adverse neurodevelopmental outcomes in exposed offspring, this work highlights the need for further investigation into PCE, particularly in larger cohorts.

The psychosocial impacts of the 15 March terrorist attack on the Christchurch Muslim community: A descriptive, cross-sectional assessment.

OBJECTIVE: On 15 March 2019, a white supremacist terrorist carried out sequential attacks on two mosques in Christchurch, New Zealand during Friday prayers. This resulted in the loss of 51 lives, 40 others sustained gunshot injuries, and there were approximately 250 survivors. This study aimed to evaluate the impacts on community members, assess clinical needs, facilitate access to appropriate interventions and provide insights into working with a traumatised and diverse population. METHODS: This cross-sectional study used semi-structured clinical interviews and self-report measures to assess social and demographic factors, mental health disorders and well-being for adult Muslims 11-32 months post-attack. RESULTS: A total of 189 participants completed assessments. The sample was diverse, representing 34 different ethnicities and participant proximity to the attack was complex, with personal and familial exposures. Elevated levels of psychological distress and psychopathology were found with 38% of participants reporting moderate/severe psychological distress on the Kessler-10, 39% reporting post-traumatic stress disorder on the post-traumatic stress disorder checklist-5, and 40% reporting poor well-being or possible depression on the World Health Organization-5 Well Being Index. Secondary stressors were also documented, as well as high scores for post-traumatic growth and the importance of faith. CONCLUSION: This study provides valuable insights into the repercussions of the Christchurch mosque attack on the affected community, describing the complexity of exposure and the substantial burden of morbidity experienced. It also highlights the high levels of social connectedness and the role of faith in promoting positive outcomes in the recovery process for this population.

Proximity of alcohol outlets and presentation to hospital by young people after self-harm: A retrospective geospatial study using the integrated data infrastructure.

OBJECTIVES: There is a well-established association between alcohol use, misuse, intoxication and self-harm, the latter of which is associated with suicide. This study aimed to better understand the association between proximity to alcohol outlets and the likelihood of young people presenting to hospital following self-harm. METHODS: This was a nationwide retrospective geospatial study using data from the New Zealand Integrated Data Infrastructure using population-level data for 10-29-year-olds for the 2018 and 2017 calendar years. Presentations to hospital following self-harm were identified using the national minimum data set. Proximity to alcohol outlets was defined in road network distance (in kilometres) and ascertained using Integrated Data Infrastructure geospatial data. Alternative measures of proximity were employed in sensitivity analyses. Complete-case two-level random intercept logistic regression models were used to estimate the relationship between alcohol outlet proximity and hospital presentation for self-harm. Adjusted models included sex, age, ethnicity, area-level deprivation, urbanicity and distance to nearest medical facility. Analyses were also stratified by urbanicity. RESULTS: Of the 1,285,368 individuals (mean [standard deviation] age 20.0 [5.9] years), 7944 (0.6%) were admitted to hospital for self-harm. Overall, the odds of presenting to hospital for self-harm significantly decreased as the distance from the nearest alcohol outlet increased, including in adjusted models (adjusted odds ratio 0.980; 95% confidence interval = [0.969-0.992]); the association was robust to changes in the measure of alcohol proximity. The effect direction was consistent across all categorisations of urbanicity, but only statistically significant in large urban areas and rural areas. CONCLUSIONS: The findings of this study show a clear association between young people's access to alcohol outlets and presentation to hospital for self-harm and may provide a mandate for government policies and universal interventions to reduce young people's access to alcohol outlets. Further research regarding causative mechanisms is needed.

The role of social support in reducing the long-term burden of cumulative childhood adversity on adulthood internalising disorder.

PURPOSE: Previous research indicates that social support is protective for the mental health outcomes of exposure to childhood adversity. However, the impact of social support as a protective factor following exposure to cumulative childhood adversity is understudied with prospective longitudinal data. The aim of this present study was to examine how social support mediates the impact of cumulative exposure to childhood adversity on internalising disorder in adulthood. METHODS: The Christchurch Health and Development Study (CHDS) is a general population birth cohort, born in 1977 and representative of Christchurch, New Zealand at the time of the cohort members' birth. The present study used a generalised estimating equations (GEE) framework to analyse direct associations between a cumulative measure of childhood adversity (CA) and internalising disorders (major depression, and any anxiety disorder), and indirect associations through social support. RESULTS: Results indicated a dose-dependent relationship between increased exposure to CA and worsened odds of a diagnosis for major depression and any anxiety disorder, respectively. There was also a significant mediating effect of social support on the direct associations between CA and both major depression (OR (95%CI) =0 .98 (0.97, 0.99), p < 001) and any anxiety disorder (OR (95%CI) = .98 (0.97, 0.99), p < 001). CONCLUSION: The findings indicate that social support reduces the impact of childhood adversity on adult mental health, and is therefore a target for future work examining potential interventions following CA.

Methamphetamine use and psychotic symptoms: findings from a New Zealand longitudinal birth cohort.

BACKGROUND: This study examined the association between methamphetamine use and psychotic symptoms in a New Zealand general population birth cohort (n = 1265 at birth). METHODS: At age 18, 21, 25, 30, and 35, participants reported on their methamphetamine use and psychotic symptoms in the period since the previous interview. Generalized estimating equations modelled the association between methamphetamine use and psychotic symptoms (percentage reporting any symptom, and number of symptoms per participant). Confounding factors included childhood individual characteristics, family socioeconomic circumstances and family functioning. Long term effects of methamphetamine use on psychotic symptoms were assessed by comparing the incidence of psychotic symptoms at age 30-35 for those with and without a history of methamphetamine use prior to age 30. RESULTS: After adjusting for confounding factors and time-varying covariate factors including concurrent cannabis use, methamphetamine use was associated with a modest increase in psychosis risk over five waves of data (adjusted odds ratio (OR) 1.33, 95% confidence interval (CI) 1.03-1.72 for the percentage measure; and IRR 1.24, 95% CI 1.02-1.50 for the symptom count measure). The increased risk of psychotic symptoms was concentrated among participants who had used at least weekly at any point (adjusted OR 2.85, 95% CI 1.21-6.69). Use of methamphetamine less than weekly was not associated with increased psychosis risk. We found no evidence for a persistent vulnerability to psychosis in the absence of continuing methamphetamine use. CONCLUSION: Methamphetamine use is associated with increased risk of psychotic symptoms in the general population. Increased risk is chiefly confined to people who ever used regularly (at least weekly), and recently.

Childhood anxious/withdrawn behaviour and later anxiety disorder: a network outcome analysis of a population cohort.

BACKGROUND: Several previous studies have identified a continuity between childhood anxiety/withdrawal and anxiety disorder (AD) in later life. However, not all children with anxiety/withdrawal problems will experience an AD in later life. Previous studies have shown that the severity of childhood anxiety/withdrawal accounts for some of the variability in AD outcomes. However, no studies to date have investigated how variation in features of anxiety/withdrawal may relate to continuity prognoses. The present research addresses this gap. METHODS: Data were gathered as part of the Christchurch Health and Development Study, a 40-year population birth cohort of 1265 children born in Christchurch, New Zealand. Fifteen childhood anxiety/withdrawal items were measured at 7-9 years and AD outcomes were measured at various interviews from 15 to 40 years. Six network models were estimated. Two models estimated the network structure of childhood anxiety/withdrawal items independently for males and females. Four models estimated childhood anxiety/withdrawal items predicting adolescent AD (14-21 years) and adult AD (21-40 years) in both males and females. RESULTS: Approximately 40% of participants met the diagnostic criteria for an AD during both the adolescent (14-21 years) and adult (21-40 years) outcome periods. Outcome networks showed that items measuring social and emotional anxious/withdrawn behaviours most frequently predicted AD outcomes. Items measuring situation-based fears and authority figure-specific anxious/withdrawn behaviour did not consistently predict AD outcomes. This applied across both the male and female subsamples. CONCLUSIONS: Social and emotional anxious/withdrawn behaviours in middle childhood appear to carry increased risk for AD outcomes in both adolescence and adulthood.

The long-term impacts of the Canterbury earthquakes on the mental health of the Christchurch Health and Development Study cohort.

OBJECTIVE: Long-term studies following disasters are rare. It is important to quantify long-term effects of disasters to determine impacts on populations over time. We therefore aim to report the long-term associations between exposure to the Canterbury earthquakes and common mental disorders, taking into account potential confounding factors. METHODS: The Christchurch Health and Development Study is a 40-year longitudinal study of a birth cohort of New Zealand children (635 males and 630 females). The Christchurch Health and Development Study includes 884 participants with data on earthquake exposure and mental health outcomes at ages 34 and 40 years. Rates of Diagnostic and Statistical Manual of Mental Disorders (4th ed.) disorders were measured categorically and using an expanded definition that included sub-syndromal symptoms. The current impact of the earthquakes is reported using 12-month prevalence data 7 years after the earthquakes. The cumulative impact of the earthquakes over the 7 years since onset is also reported. RESULTS: There was a linear trend towards increasing rates of disorder with increasing exposure to the earthquakes. After adjusting for covariates, the 12-month prevalence of anxiety disorder symptoms was significantly increased (p = 0.003). The earthquakes were also associated with cumulative increases in symptoms of post-traumatic stress disorder (p < 0.001), anxiety disorder (p = 0.016), nicotine dependence (p = 0.012), and the total number of disorders (p = 0.039). CONCLUSION: The Canterbury earthquakes were associated with persistent increases in Anxiety Disorder symptoms 7 years after their onset. The earthquakes were also associated with cumulative increases in symptoms of common psychiatric disorders. The magnitude of these effects is small, may no longer be clinically significant and has decreased over time.

DNA methylation analysis using bisulphite-based amplicon sequencing of individuals exposed to maternal tobacco use during pregnancy, and offspring conduct problems in childhood and adolescence.

Maternal tobacco smoking during pregnancy is a large driver of health inequalities and a higher prevalence of conduct problem (CP) has been observed in exposed offspring. Further, maternal tobacco use during pregnancy can also alter offspring DNA methylation. However, currently, limited molecular evidence has been found to support this observation. Thus we aim to examine the association between maternal tobacco use in pregnancy and offspring CP, to determine whether offspring CP is mediated by tobacco exposure-induced DNA methylation differences. Understanding the etiology of the association between maternal tobacco use and offspring CP will be crucial in the early identification and treatment of CP in children and adolescents. Here, a sub group of N =96 individuals was sourced from the Christchurch Health and Development Study, a longitudinal birth cohort studied for over 40 years in New Zealand. Whole blood samples underwent bisulphite-based amplicon sequencing at 10 loci known to play a role in neurodevelopment, or which had associations with CP phenotypes. We identified significant (P CYP1A1 , ASH2L and MEF2C in individuals with CP who were exposed to tobacco in utero . We conclude that environmentally-induced DNA methylation differences could play a role in the observed link between maternal tobacco use during pregnancy and childhood/adolescent CP. However, larger sample sizes are needed to produce an adequate amount of power to investigate this interaction further.

The association between alcohol use disorder and suicidal ideation in a New Zealand birth cohort.

BACKGROUND: Alcohol use disorder is associated with increased suicide risk; however, both alcohol use disorder and suicide share risk factors which must be accounted for in order to understand this relationship. This study aimed to explore the longitudinal relationship between alcohol use disorder and suicidal ideation in adulthood, while accounting for both child background and adult covariate factors. METHOD: Data were collected from the Christchurch Health and Development Study, a birth cohort of 1265 children born in Christchurch (New Zealand) in mid-1977. Alcohol use disorder (operationalised as alcohol abuse and alcohol dependence) was quantified between age 18 and 40 in five data waves. The outcome measure suicidal ideation was reported over the same time periods. Childhood confounding variables were controlled for, as well as time-dynamic covariates collected in adulthood, including internalising disorders, distress due to relationship dissolutions and other substance use disorders. RESULTS: The association between alcohol abuse and suicidal ideation was not statistically significant before or after adjusting for childhood confounding and adulthood covariate factors, when compared to no alcohol disorder. However, the association between alcohol dependence and suicidal ideation was significant both before and after adjustment (unadjusted odds ratio = 2.89, 95% confidence interval = [2.09, 3.99]; adjusted odds ratio = 1.52, 95% confidence interval = [1.04, 2.23]), when compared to no alcohol disorder. Furthermore, alcohol dependence remained significant when compared to alcohol abuse (unadjusted odds ratio = 2.33, 95% confidence interval = [1.61, 3.37]; adjusted odds ratio = 1.54, 95% confidence interval = [1.00, 2.37]). CONCLUSION: This analysis found an association between alcohol dependence and suicidal ideation within a New Zealand birth cohort, which persists even after adjustment for childhood confounding and adulthood covariate factors. Given the high rates of suicide and heavy drinking within the New Zealand population, any comprehensive national or regional suicide prevention plan should seek to reduce risky alcohol consumption at an individual and population level, as this represents a modifiable risk factor for suicide.

New Zealand Women's Experience of Intimacy Within Heterosexual Relationships: Influence of Partners' Perceived Pornography Use.

The association between women's levels of relationship intimacy and how frequently their partner viewed pornography was examined in a community sample of 136 NZ heterosexual women. Controlling for age, ethnicity and education, partner use of pornography was significantly negatively correlated with emotional, sexual, intellectual and recreational intimacy, but not social intimacy. Women's attitudes toward pornography did not mediate any of these associations. However, significant moderation effects were found: women with more negative attitudes toward pornography reported lower rates of emotional and social intimacy when their partner was believed to be viewing pornography weekly or more, but not when this frequency was less. No association was found for women with less negative attitudes toward pornography. These findings indicate that pornography may be detrimental to relationship intimacy for women with strongly negative attitudes toward it.